Cargando…

Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging

Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, wh...

Descripción completa

Detalles Bibliográficos
Autores principales: Bertrand, Christelle, Blanchet, Emilie, Pessemesse, Laurence, Annicotte, Jean Sébastien, Feillet-Coudray, Christine, Chabi, Béatrice, Levin, Jonathan, Fajas, Lluis, Cabello, Gérard, Wrutniak-Cabello, Chantal, Casas, François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787095/
https://www.ncbi.nlm.nih.gov/pubmed/24098680
http://dx.doi.org/10.1371/journal.pone.0075111
_version_ 1782286140263366656
author Bertrand, Christelle
Blanchet, Emilie
Pessemesse, Laurence
Annicotte, Jean Sébastien
Feillet-Coudray, Christine
Chabi, Béatrice
Levin, Jonathan
Fajas, Lluis
Cabello, Gérard
Wrutniak-Cabello, Chantal
Casas, François
author_facet Bertrand, Christelle
Blanchet, Emilie
Pessemesse, Laurence
Annicotte, Jean Sébastien
Feillet-Coudray, Christine
Chabi, Béatrice
Levin, Jonathan
Fajas, Lluis
Cabello, Gérard
Wrutniak-Cabello, Chantal
Casas, François
author_sort Bertrand, Christelle
collection PubMed
description Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43−/− mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43−/− mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43−/− mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes.
format Online
Article
Text
id pubmed-3787095
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37870952013-10-04 Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging Bertrand, Christelle Blanchet, Emilie Pessemesse, Laurence Annicotte, Jean Sébastien Feillet-Coudray, Christine Chabi, Béatrice Levin, Jonathan Fajas, Lluis Cabello, Gérard Wrutniak-Cabello, Chantal Casas, François PLoS One Research Article Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43−/− mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43−/− mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43−/− mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes. Public Library of Science 2013-09-30 /pmc/articles/PMC3787095/ /pubmed/24098680 http://dx.doi.org/10.1371/journal.pone.0075111 Text en © 2013 Bertrand et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bertrand, Christelle
Blanchet, Emilie
Pessemesse, Laurence
Annicotte, Jean Sébastien
Feillet-Coudray, Christine
Chabi, Béatrice
Levin, Jonathan
Fajas, Lluis
Cabello, Gérard
Wrutniak-Cabello, Chantal
Casas, François
Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging
title Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging
title_full Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging
title_fullStr Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging
title_full_unstemmed Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging
title_short Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging
title_sort mice lacking the p43 mitochondrial t3 receptor become glucose intolerant and insulin resistant during aging
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3787095/
https://www.ncbi.nlm.nih.gov/pubmed/24098680
http://dx.doi.org/10.1371/journal.pone.0075111
work_keys_str_mv AT bertrandchristelle micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT blanchetemilie micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT pessemesselaurence micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT annicottejeansebastien micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT feilletcoudraychristine micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT chabibeatrice micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT levinjonathan micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT fajaslluis micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT cabellogerard micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT wrutniakcabellochantal micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging
AT casasfrancois micelackingthep43mitochondrialt3receptorbecomeglucoseintolerantandinsulinresistantduringaging